全文获取类型
收费全文 | 2373篇 |
免费 | 131篇 |
国内免费 | 2篇 |
专业分类
2506篇 |
出版年
2022年 | 8篇 |
2021年 | 22篇 |
2020年 | 17篇 |
2019年 | 23篇 |
2018年 | 39篇 |
2017年 | 17篇 |
2016年 | 48篇 |
2015年 | 91篇 |
2014年 | 90篇 |
2013年 | 166篇 |
2012年 | 161篇 |
2011年 | 145篇 |
2010年 | 85篇 |
2009年 | 112篇 |
2008年 | 160篇 |
2007年 | 166篇 |
2006年 | 145篇 |
2005年 | 163篇 |
2004年 | 149篇 |
2003年 | 142篇 |
2002年 | 129篇 |
2001年 | 22篇 |
2000年 | 22篇 |
1999年 | 23篇 |
1998年 | 29篇 |
1997年 | 29篇 |
1996年 | 30篇 |
1995年 | 26篇 |
1994年 | 14篇 |
1993年 | 23篇 |
1992年 | 12篇 |
1991年 | 17篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 17篇 |
1986年 | 8篇 |
1985年 | 15篇 |
1984年 | 7篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1976年 | 9篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1965年 | 4篇 |
1963年 | 3篇 |
排序方式: 共有2506条查询结果,搜索用时 15 毫秒
91.
Hiroya Miyamoto Eri Katsuyama Yoshiteru Miyauchi Hiroko Hoshi Kana Miyamoto Yuiko Sato Tami Kobayashi Ryotaro Iwasaki Shigeyuki Yoshida Tomoaki Mori Hiroya Kanagawa Atsuhiro Fujie Wu Hao Hideo Morioka Morio Matsumoto Yoshiaki Toyama Takeshi Miyamoto 《The Journal of biological chemistry》2012,287(39):32479-32484
92.
Reactive oxygen species (ROS) have the potential to damage cellular components, such as protein, resulting in loss of function and structural alteration of proteins. The oxidative process affects a variety of side amino acid groups, some of which are converted to carbonyl compounds. We have previously shown that a prostaglandin D2 metabolite, 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), is the potent inducer of intracellular oxidative stress on human neuroblastoma SH-SY5Y cells [Kondo, M., Oya-Ito, T., Kumagai, T., Osawa, T., and Uchida, K. (2001) Cyclopentenone prostaglandins as potential inducers of intracellular oxidative stress, J. Biol. Chem. 276, 12076-12083]. In the present study, to elucidate the molecular mechanism underlying the oxidative stress-mediated cell degeneration, we analyzed the protein carbonylation on SH-SY5Y cells when these cells were submitted to an endogenous inducer of ROS production. Upon exposure of SH-SY5Y cells to this endogenous electrophile, we observed significant accumulation of protein carbonyls within the cells. Proteomic analysis of oxidation-sensitive proteins showed that the major intracellular target of protein carbonylation was one of the regulatory subunits in 26 S proteasome, S6 ATPase. Accompanied by a dramatic increase in protein carbonyls within S6 ATPase, the electrophile-induced oxidative stress exerted a significant decrease in the S6 ATPase activities and a decreased ability of the 26 S proteasome to degrade substrates. Moreover, in vitro oxidation of 26 S proteasome with a metal-catalyzed oxidation system also confirmed that S6 ATPase represents the most oxidation-sensitive subunit in the proteasome. These and the observation that down-regulation of S6 ATPase by RNA interference resulted in the enhanced accumulation of ubiquitinated proteins suggest that S6 ATPase is a molecular target of ROS under conditions of electrophile-induced oxidative stress and that oxidative modification of this regulatory subunit of proteasome may be functionally associated with the altered recognition and degradation of proteasomal substrates in the cells. 相似文献
93.
94.
Phosphoglucomutase (PGM, EC 2.7.5.1) is one of the enzymes constituting the carbohydrate synthesis pathway in higher plants. It catalyzes the reversible conversion of glucose 6-phosphate (Glc6P) to glucose 1-phosphate (Glc1P). Previously, metabolic turnover analysis using (13)CO(2) in tobacco leaves demonstrated that conversion of Glc6P to Glc1P may limit carbon flow into carbohydrate synthesis. In order to assess the effects of PGM, Arabidopsis thaliana cytosolic or plastidial PGM was expressed under the control of cauliflower mosaic virus 35S promoter in tobacco plants (Nicotiana tabacum cv. Xanthi) and phenotypic analysis was performed. The transgenic plants expressing Arabidopsis plastidial PGM showed 3.5-8.2-fold higher PGM activity than that of wild-type, and leaf starch and sucrose contents increased 2.3-3.2-fold and 1.3-1.4-fold, respectively over wild-type levels. In vivo(13)C-labeling experiments indicated that photosynthetically fixed carbon in the transgenic plants could be converted faster to Glc1P and adenosine 5'-diphosphate glucose than in wild-type, suggesting that elevation of plastidial PGM activity should accelerate conversion of Glc6P to Glc1P in chloroplasts and increase carbon flow into starch. On the other hand, transgenic plants expressing Arabidopsis cytosolic PGM showed a 2.1-3.4-fold increase in PGM activity over wild-type and a decrease of leaf starch content, but no change in sucrose content. These results suggest that plastidial PGM limits photosynthetic carbon flow into starch. 相似文献
95.
96.
Yumiko I. Matsuishi Hiroki Kato Keiji Masuda Haruyoshi Yamaza Yuta Hirofuji Hiroshi Sato Hiroko Wada Tamotsu Kiyoshima Kazuaki Nonaka 《Biochemical and biophysical research communications》2018,495(2):1655-1660
Undifferentiated odontogenic epithelium and dental papilla cells differentiate into ameloblasts and odontoblasts, respectively, both of which are essential for tooth development. These differentiation processes involve dramatic functional and morphological changes of the cells. For these changes to occur, activation of mitochondrial functions, including ATP production, is extremely important. In addition, these changes are closely related to mitochondrial fission and fusion, known as mitochondrial dynamics. However, few studies have focused on the role of mitochondrial dynamics in tooth development. The purpose of this study was to clarify this role. We used mouse tooth germ organ cultures and a mouse dental papilla cell line with the ability to differentiate into odontoblasts, in combination with knockdown of the mitochondrial fission factor, dynamin related protein (DRP)1. In organ cultures of the mouse first molar, tooth germ developed to the early bell stage. The amount of dentin formed under DRP1 inhibition was significantly larger than that of the control. In experiments using a mouse dental papilla cell line, differentiation into odontoblasts was enhanced by inhibiting DRP1. This was associated with increased mitochondrial elongation and ATP production compared to the control. These results suggest that DRP1 inhibition accelerates dentin formation through mitochondrial elongation and activation. This raises the possibility that DRP1 might be a therapeutic target for developmental disorders of teeth. 相似文献
97.
98.
Hiroko Tanabe Keisuke Fujii Motoki Kouzaki 《Journal of electromyography and kinesiology》2012,22(6):975-982
The purpose of this study was to detect the characteristics of center of pressure (COP) movement during tiptoe standing (TS) compared to quiet standing (QS). Eight healthy subjects were asked to perform QS and TS on a force platform. During standing, surface electromyograms (EMGs) were recorded from the soleus (SOL), flexor hallucis brevis (FHB), medial gastrocnemius (MG), lateral gastrocnemius (LG), and tibialis anterior (TA) muscles. The path length and rectangular area of the COP trajectory were significantly larger during TS than during QS. In contrast, irrespective of standing condition, the scaling coefficients in the short and long regions were above and below 0.5, respectively. The coherence spectrum between the COP and EMG from the SOL and FHB muscles was statistically significant during TS at frequencies up to 17 Hz, while that for the QS was only significant below 1 Hz. In conclusion, the control of COP movement during TS was similar to that during QS despite large COP fluctuations during TS. Our results suggest that unstable posture during TS is compensated for by the activities of the SOL and FHB muscles, which enhance postural control. 相似文献
99.
Abe R Caaveiro JM Kozuka-Hata H Oyama M Tsumoto K 《The Journal of biological chemistry》2012,287(20):16477-16487
Iron is an essential nutrient for the proliferation of Staphylococcus aureus during bacterial infections. The iron-regulated surface determinant (Isd) system of S. aureus transports and metabolizes iron porphyrin (heme) captured from the host organism. Transportation of heme across the thick cell wall of this bacterium requires multiple relay points. The mechanism by which heme is physically transferred between Isd transporters is largely unknown because of the transient nature of the interactions involved. Herein, we show that the IsdC transporter not only passes heme ligand to another class of Isd transporter, as previously known, but can also perform self-transfer reactions. IsdA shows a similar ability. A genetically encoded photoreactive probe was used to survey the regions of IsdC involved in self-dimerization. We propose an updated model that explicitly considers self-transfer reactions to explain heme delivery across the cell wall. An analogous photo-cross-linking strategy was employed to map transient interactions between IsdC and IsdE transporters. These experiments identified a key structural element involved in the rapid and specific transfer of heme from IsdC to IsdE. The resulting structural model was validated with a chimeric version of the homologous transporter IsdA. Overall, our results show that the ultra-weak interactions between Isd transporters are governed by bona fide protein structural motifs. 相似文献
100.